This invention relates to compounds of the formula (I), ##STR2##
wherein R is (C.sub.1 -C.sub.5) alkyl or CH.sub.3 (CH.sub.2).sub.n CO--; and n is 1, 2, 3 or 4, which are useful in the treatment of diseases, disorders and adverse conditions caused by Helicobacter pylori and are particularly useful in the treatment of gastroduodenal disorders, diseases and adverse conditions caused thereby. This invention further relates to a method of treating Helicobacter pylori induced disorders, diseases and adverse conditions and particularly gastroduodenal disorders, diseases and adverse conditions in a mammal comprising administering to said mammal the compound of formula (II), ##STR3##
hereinafter referred to as spirolaxine.
Spirolaxine is a known antibiotic which can be isolated from the microorganism Chrysosporium pruinosum ATCC 15155. Spirolaxine is reported to have weak bacteriostatic activity against Bacillus cereus, Bacillus subtilis and Escherichia coli. Arnone et al., Phytochemistry, 1990, 29, 613-616. Further, spirolaxine is reported to have no antifungal activity against Aspergillus niger, Botrytis cinerea, Cladosporium cucumerinum, Ophiostoma ulmi and Saccharomyces cerevisiae. Arnone et al., Phytochemistry, 1990, 29, 613-616.
Gastric and duodenal ulcers affect a significant portion of the human population worldwide. Currently, the usual treatment for both gastric and duodenal ulcers involves treatment of the patient with H.sub.2 blockers. While generally effective in healing ulcers, ulcer relapse occurs in up to 90% of patients within a year of discontinuing H.sub.2 blocker therapy. O'Connor, H. J., Postgraduate Medical Journal, 1992, 68, 549-57. Thus, patients must continue the treatment for many years or risk a recurrence of the ulcer. It is now known that ulcer healing drugs such as colloidal bismuth subcitrate (CBS) are helicobactericidal and as such CBS is used in combination with H.sub.2 blockers to treat ulcers. O'Connor, ibid. Additionally, CBS, an H.sub.2 blocker and amoxicillin have been used in combination to treat ulcer patients. O'Connor, ibid.
Helicobacter pylori has recently been demonstrated to be a major causative agent in gastric and duodenal ulcers and other gastroduodenal disorders, diseases and adverse conditions. Thus, antibiotic therapy to eliminate Helicobacter pylori from the gastroduodenal tract would remove the root cause of said gastroduodenal disorders, diseases and adverse conditions and eliminate the need for an ulcer patient to continue long and costly treatment with H.sub.2 blockers and the like. None of the foregoing treatments are capable of 100% eradication of Helicobacter pylori.
Applicants have now found that spirolaxine and the spirolaxine ethers of the instant invention are potent helicobactericidal compounds. A helicobactericidal compound is a compound which kills Helicobacter pylori. Therefore spirolaxine and the spirolaxine ethers of formula (I) of the instant invention possess utility in treating gastroduodenal disorders, diseases and adverse conditions and particularly in treating gastric and duodenal ulcer and preventing gastric cancer.